title: Isoangustone A suppresses mesangial fibrosis and inflammation in human renal mesangial cells.
abstract: Development of diabetic nephropathy with fibrosis is associated with hypereglycemia-linked inflammation. Increased levels of proinflammatory factors have been found in diabetic patients with nephropathy. The present study was to test the hypothesis that isoangustone A, a novel compound present in licorice, can inhibit renal fibrosis and inflammation inflamed by high glucose (HG) in human mesangial cells through disturbing transforming growth factor β (TGF-β) and nuclear facor κB (NF-κB) pathways. Serum-starved mesangial cells were cultured in 33 mmol/L glucose media. Cells were treated with 1-20 μmol/L isoangustone A isolated from Glycyrrhiza uralensis licorice for three days. Exposure of cells to HG elevated connective tissue growth factor and collagen production, which was dose-dependently reversed by isoangustone A. Isoangustone A boosted HG-plummeted membrane type matrix metalloproteinase (MMP)-1 expression and diminished HG-elevated tissue inhibitor of MMP-2 expression. HG activated mesangial TGF-β1-SMAD-responsive signaling, which was repealed by ≥10 μmol/L isoangustone A. Furthermore, HG upregulated intracellular cell adhesion molecule-1 (ICAM-1) level and monocyte chemoattractant protein-1 (MCP-1) mRNA expression, and such increases were dose-dependently suppressed by isoangustone A most likely through hampering TGF-β signaling pathways. Blockade of NF-κB signaling appeared to be responsible for attenuating HG-triggered induction of ICAM-1 and MCP-1. Our findings provide the first evidence that isoangustone A dampens mesangial sclerosis associated with inflammation in response to HG through hindering TGF-β and NF-κB signaling.
authors.affiliation: Department of Food and Nutrition, Hallym University, Chuncheon, Kangwon-do 200-702, South Korea.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Soon Sung
authors.initials: SS
authors.lastname: Lim
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Ju-Hyun
authors.initials: JH
authors.lastname: Gong
authors.forename: Daekeun
authors.initials: D
authors.lastname: Shin
authors.forename: Il-Jun
authors.initials: IJ
authors.lastname: Kang
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D005355:Fibrosis; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000139:chemically induced*; D007529:Isoflavones / Q000494:pharmacology*
chemical_list: D007529:Isoflavones; C551631:isoangustone A